Weak Signal Research Articles

An intelligent fluorescence sensing platform based on entropy-driven toehold-mediated strand displacement cycle reaction for point-of-care testing of miRNA

BackgroundMicroRNA (miRNA) has gradually become an emerging biomarker for early diagnosis and prognosis of various diseases due to its specific gene expression and high stability. With the development of molecular diagnosis and point-of-care testing (POCT) technology, developing simple, fast, sensitive, efficient, and low-cost miRNA sensors is of great significance for clinical applications and emergency rapid diagnosis. At present, entropy-driven toehold mediated chain displacement reaction, as a promising enzyme free isothermal amplification technique, is an important tool for ultra-sensitive biosensing applications. ResultsIn this study, we used gold nanoparticles (AuNPs) as carriers and quenchers, modified them using self-assembled triple chain composite substrates AuNPs@A@B1/B2, and used dual reporter molecules for cascade cyclic amplification to amplify fluorescence signals, which proposed a fluorescent biosensor based on this reaction and build an intelligent fluorescence sensing platform for rapid detection of miRNA. We designed a highly specific self-programmable sensor using the acute ischemic stroke (AIS) biomarker miRNA-125a-5p as a sample, and achieved sensitive detection of miRNA in the range of 0.01 μM∼10 μ M under optimal conditions. It broke through the traditional detection limitations of weak signals and liberated the fluorescence detection environment. SignificanceIn summary, this creative miRNA biosensor combined with POCT has demonstrated extraordinary detection potential, broad application prospects in the early diagnosis and prognosis monitoring of AIS, provides a novel miRNA universal detection strategy for the fields of biological and life sciences.

Matrix Completion When Missing Is Not at Random and Its Applications in Causal Panel Data Models

This article develops an inferential framework for matrix completion when missing is not at random and without the requirement of strong signals. Our development is based on the observation that if the number of missing entries is small enough compared to the panel size, then they can be estimated well even when missing is not at random. Taking advantage of this fact, we divide the missing entries into smaller groups and estimate each group via nuclear norm regularization. In addition, we show that with appropriate debiasing, our proposed estimate is asymptotically normal even for fairly weak signals. Our work is motivated by recent research on the Tick Size Pilot Program, an experiment conducted by the Security and Exchange Commission (SEC) to evaluate the impact of widening the tick size on the market quality of stocks from 2016 to 2018. While previous studies were based on traditional regression or difference-in-difference methods by assuming that the treatment effect is invariant with respect to time and unit, our analyses suggest significant heterogeneity across units and intriguing dynamics over time during the pilot program. Supplementary materials for this article are available online, including a standardized description of the materials available for reproducing the work.

Europeans and Americans of European origin show differences between their biological pathways related to the major histocompatibility complex

In this study, we analysed biological pathway diversity among Europeans and Northern Americans of European origin, the groups of people that share a common genetic ancestry but live in different geographic regions. We used a novel complex approach for analysing genomic data: we studied the total effects of multiple weak selection signals, accumulated from independent SNPs within a pathway. We found significant differences between immunity-related biological pathways from the two groups. All identified pathways included genes belonging to the major histocompatibility complex (MHC) system, which plays an important role in adaptive immune responses. We suggest that the ways of evolution were different for the MHC-I and MHC-II gene groups at least in Europeans and Americans of European origin. We hypothesise that the observed variability between the two populations was triggered by selection pressures due to the different pathogen landscapes and pathogen loads on the two continents. Our findings can be important for epidemic prevention and control, as well as for analysing processes related to allergies, organ transplantation, and autoimmune diseases.

Deterministic analysis of stochastic FHN systems based on Gaussian decoupling

This paper systematically explores the deterministic characteristics of FitzHugh-Nagumo (FHN) systems’ response to synaptic noise in statistical sense. With the help of Gauss decoupling approximation, two substitute systems of FHN systems’ response to synaptic noise are established by ignoring the cumulants higher than the second order, and the feasibilities of using the substitute systems for response analysis are demonstrated through error analysis. Then, the deterministic analyses of FHN systems with synaptic noise are carried out by means of the two substitute systems. Numerical results show that whether it is the neuronal system or the network system, the synaptic noise can effectively regulate its dynamics, and induce the mode transitions of discharge activity. Based on the class II excitability of FHN neurons, the system activity has a nonlinear dependence on the noise parameter and the other variables of interest. Particularly, the synaptic noise not only makes the neuronal system transition from low-level to high-level narrow-amplitude oscillation by competing with the input signal, but also contributes to the response or detection of this system to weak input signals. This study reveals the deterministic characteristics of FHN systems with synaptic noise, which can provide a reference for the large-scale analysis.

Tracing the electron transport behavior in quantum-dot light-emitting diodes via single photon counting technique

The electron injection and transport behavior are of vital importance to the performance of quantum-dot light-emitting diodes. By simultaneously measuring the electroluminescence-photoluminescence of the quantum-dot light-emitting diodes, we identify the presence of leakage electrons which leads to the discrepancy of the electroluminescence and the photoluminescence roll-off. To trace the transport paths of the leakage electrons, a single photon counting technique is developed. This technique enables us to detect the weak photon signals and thus provides a means to visualize the electron transport paths at different voltages. The results show that, the electrons, except those recombining within the quantum-dots, leak to the hole transport layer or recombine at the hole transport layer/quantum-dot interface, thus leading to the reduction of efficiency. By reducing the amount of leakage electrons, quantum-dot light-emitting diode with an internal power conversion efficiency of over 98% can be achieved.

Steady-state magnon entanglement and backaction-evading of a weak magnetic signal via two-tone modulated cavity electromagnonics

Cavity electromagnonics explore the coupling between microwave cavity fields and magnons in micromagnets. This field has emerged as a promising platform for probing fundamental aspects of quantum mechanics and advancing quantum technologies. This paper investigates a scheme involving two-tone frequency modulation to engineer simultaneous magnon-photon two-mode squeezing and beam-splitter-like interactions. We demonstrate that this scheme enables the direct generation of macroscopic magnonic squeezed and entangled states. Moreover, it facilitates ultra-sensitive magnon-based magnetic field sensing through quantum non-demolition (QND) interactions between magnons and photons. The present scheme provides promising opportunities for generating macroscopic nonclassical quantum states in solid magnetic materials and developing spintronics-related quantum devices.

High‐Performance Single‐Microplate Perovskite Photodetectors Based on Polyvinyl Alcohol Filled Planar Electrodes for Weak‐Light Imaging and Pixel Integration

AbstractPhotoconductors featuring an individual micro/nano‐crystal as the photoactive channel hold the great promise for next‐generation integrated optoelectronics. Meanwhile, the gain aiming for signal amplification without an extra amplifier, the fast response for fast data transfer, and low dark current for weak signal acquisition are highly desirable in integrated optoelectronics, but are inherent trade‐off in traditional photoconductors. Herein, the study demonstrates a single‐microplate MAPbI3 photoconductor based on polyvinyl alcohol‐filled planar electrodes that can simultaneously achieve excellent performance on these parameters. The superior performance can be attributed to the exquisite design of filling the device channel gap with polyvinyl alcohol. This deep‐work‐function transparent polyvinyl alcohol can not only passivate surface defects of the perovskite microplate by hydrogen bonding, but also form a heterojunction with top perovskites to induce a depleted channel. Resultant single‐microplate photodetectors exhibit exceptional performance characteristics including ultra‐low noise‐equivalent power of 0.19 fW Hz−1/2, high specific detectivity of 3.68 × 1014 Jones, fast response of 3.2 µs, high EQE‐bandwidth over 107 Hz, as well as excellent stability. More importantly, single‐microplate MAPbI3 photoconductors demonstrate ultra‐weak‐light imaging ability surpassing silicon counterparts. Furthermore, the successful integration of their microplate pixels showcases the promising prospect for integrated optoelectronics.

A taxon-rich and genome-scale phylogeny of Opisthokonta.

Ancient divergences within Opisthokonta-a major lineage that includes organisms in the kingdoms Animalia, Fungi, and their unicellular relatives-remain contentious. To assess progress toward a genome-scale Opisthokonta phylogeny, we conducted the most taxon rich phylogenomic analysis using sets of genes inferred with different orthology inference methods and established the geological timeline of Opisthokonta diversification. We also conducted sensitivity analysis by subsampling genes or taxa from the full data matrix based on filtering criteria previously shown to improve phylogenomic inference. We found that approximately 85% of internal branches were congruent across data matrices and the approaches used. Notably, the use of different orthology inference methods was a substantial contributor to the observed incongruence: analyses using the same set of orthologs showed high congruence of 97% to 98%, whereas different sets of orthologs resulted in somewhat lower congruence (87% to 91%). Examination of unicellular Holozoa relationships suggests that the instability observed across varying gene sets may stem from weak phylogenetic signals. Our results provide a comprehensive Opisthokonta phylogenomic framework that will be useful for illuminating ancient evolutionary episodes concerning the origin and diversification of the 2 major eukaryotic kingdoms and emphasize the importance of investigating effects of orthology inference on phylogenetic analyses to resolve ancient divergences.

Orbital Adipose Tissue: The Optimal Control for Back-Table Fluorescence Imaging of Orbital Tumors.

Control tissue is essential for ensuring the precision of semiquantitative analysis in back-table fluorescence imaging. However, there remains a lack of agreement on the appropriate selection of control tissues. To evaluate the back-table fluorescence imaging performance of different normal tissues and identify the optimal normal tissue, a cohort of 39 patients with orbital tumors were enrolled in the study. Prior to surgery, these patients received indocyanine green (ICG) and following resection, 43 normal control tissues (34 adipose tissues, 3 skin tissues, 3 periosteal tissues, and 3 muscle tissues) were examined using back-table fluorescence imaging. The skin tissue demonstrated significantly elevated fluorescence intensity in comparison to the diseased tissue, whereas the muscle tissue exhibited a broad range and standard deviation of fluorescence signal intensity. Conversely, the adipose and periosteum displayed weak fluorescence signals with a relatively consistent distribution. Additionally, no significant correlations were found between the signal-to-background ratio (SBR) of adipose tissue and patients' ages, genders, weights, disease duration, tumor origins, dosing of administration of ICG infusion, and the time interval between ICG infusion and surgery. However, a positive correlation was observed between the SBR of adipose tissue and its size, with larger adipose tissues (>1 cm) showing an average SBR 27% higher than smaller adipose tissues (≤1 cm). In conclusion, the findings of this study demonstrated that adipose tissue consistently exhibited homogeneous hypofluorescence during back-table fluorescence imaging, regardless of patient clinical variables or imaging parameters. The size of the adipose tissue was identified as the primary factor influencing its fluorescence imaging characteristics, supporting its utility as an ideal control tissue for back-table fluorescence imaging.

Localization and Tissue Tropism of Ostreid Herpesvirus 1 in Blood Clam Anadara broughtonii.

OsHV-1 caused detrimental infections in a variety of bivalve species of major importance to aquaculture worldwide. Since 2012, there has been a notable increase in the frequency of mass mortality events of the blood clam associated with OsHV-1 infection. The pathological characteristics, tissue and cellular tropisms of OsHV-1 in A. broughtonii remain unknown. In this study, we sought to investigate the distribution of OsHV-1 in five different organs (mantle, hepatopancreas, gill, foot, and adductor muscle) of A. broughtonii by quantitative PCR, histopathology and in situ hybridization (ISH), to obtain insight into the progression of the viral infection. Our results indicated a continuous increase in viral loads with the progression of OsHV-1 infection, reaching a peak at 48 h or 72 h post-infection according to different tissues. Tissue damage and necrosis, as well as colocalized OsHV-1 ISH signals, were observed primarily in the connective tissues of various organs and gills. Additionally, minor tissue damage accompanied by relatively weak ISH signals was detected in the foot and adductor muscle, which were filled with muscle tissue. The predominant cell types labeled by ISH signals were infiltrated hemocytes, fibroblastic-like cells, and flat cells in the gill filaments. These results collectively illustrated the progressive alterations in pathological confusion and OsHV-1 distribution in A. broughtonii, which represent most of the possible responses of cells and tissues to the virus.

Research on the Depth Image Reconstruction Algorithm Using the Two-Dimensional Kaniadakis Entropy Threshold.

The photon-counting light laser detection and ranging (LiDAR), especially the Geiger mode avalanche photon diode (Gm-APD) LiDAR, can obtain three-dimensional images of the scene, with the characteristics of single-photon sensitivity, but the background noise limits the imaging quality of the laser radar. In order to solve this problem, a depth image estimation method based on a two-dimensional (2D) Kaniadakis entropy thresholding method is proposed which transforms a weak signal extraction problem into a denoising problem for point cloud data. The characteristics of signal peak aggregation in the data and the spatio-temporal correlation features between target image elements in the point cloud-intensity data are exploited. Through adequate simulations and outdoor target-imaging experiments under different signal-to-background ratios (SBRs), the effectiveness of the method under low signal-to-background ratio conditions is demonstrated. When the SBR is 0.025, the proposed method reaches a target recovery rate of 91.7%, which is better than the existing typical methods, such as the Peak-picking method, Cross-Correlation method, and the sparse Poisson intensity reconstruction algorithm (SPIRAL), which achieve a target recovery rate of 15.7%, 7.0%, and 18.4%, respectively. Additionally, comparing with the SPIRAL, the reconstruction recovery ratio is improved by 73.3%. The proposed method greatly improves the integrity of the target under high-background-noise environments and finally provides a basis for feature extraction and target recognition.

Conorphin-66 produces peripherally restricted antinociception via the kappa-opioid receptor with limited side effects

With the current unmet demand for effective pain relief, analgesics without major central adverse effects are highly appealing, such as peripherally restricted kappa-opioid receptor (KOR) agonists. In this study, Conorphin-66, an analog of the selective KOR peptide agonist Conorphin T, was pharmacologically characterized in a series of experiments, with CR845 serving as the reference compound. Firstly, in vitro functional assay indicated that Conorphin-66 selectively activates KOR and exhibits weak β-arrestin2 signaling bias (−1.54 versus −4.35 for CR845). Additionally, subcutaneous Conorphin-66 produced potent antinociception in mouse pain models with ED50 values ranged from 0.02 to 3.28 μmol/kg, including tail-flick test, post-operative pain, formalin pain, and acetic acid-induced visceral pain. Similarly, CR845 exert potent antinociception in mouse pain models ranged from 0.15 to 1.47 μmol/kg. Notably, antagonism studies revealed that the analgesic effects of Conorphin-66 were mainly mediated by the peripheral KOR. Furthermore, Conorphin-66 produced non-tolerance-forming antinociception over 8 days. Unlike CR845, subcutaneous Conorphin-66 did not promote the sedation, anxiogenic effects, depressive-like effects, but did exhibit diuretic activity. Further study showed that Conorphin-66 does not have apparent antipruritic effects in an acute itch model. Overall, Conorphin-66 emerges as a novel peripherally restricted KOR agonist that produced potent antinociception with reduced side effects.

Spectral Detection of a Weak Frequency Band Signal Based on the Pre-Whitening Scale Transformation of Stochastic Resonance in a Symmetric Bistable System in a Parallel Configuration

Spectral Detection of a Weak Frequency Band Signal Based on the Pre-Whitening Scale Transformation of Stochastic Resonance in a Symmetric Bistable System in a Parallel Configuration

Data-driven optimal shrinkage of singular values under high-dimensional noise with separable covariance structure with application

We develop a data-driven optimal shrinkage algorithm, named extended OptShrink (eOptShrink), for matrix denoising with high-dimensional noise and a separable covariance structure. This noise is colored and dependent across samples. The algorithm leverages the asymptotic behavior of singular values and vectors of the noisy data's random matrix. Our theory includes the sticking property of non-outlier singular values, delocalization of weak signal singular vectors, and the spectral behavior of outlier singular values and vectors. We introduce three estimators: a novel rank estimator, an estimator for the spectral distribution of the pure noise matrix, and the optimal shrinker eOptShrink. Notably, eOptShrink does not require estimating the noise's separable covariance structure. We provide a theoretical guarantee for these estimators with a convergence rate. Through numerical simulations and comparisons with state-of-the-art optimal shrinkage algorithms, we demonstrate eOptShrink's application in extracting maternal and fetal electrocardiograms from single-channel trans-abdominal maternal electrocardiograms.

Efficient Redirection of Trapped Broad-Band Fluorescence from Substrates into Free Space Using c-Si Metasurfaces.

Fluorescent dye films on transparent substrates are essential for OLEDs, flexible displays, X-ray detection, and wireless optical communications. However, their efficiency is often hampered by fluorescence trapping due to total internal reflection (TIR) and waveguiding. This study tackles this longstanding challenge by reconceptualizing the integration of dye films with nanoantenna metasurfaces. Traditional methods involve directly spin-coating films onto c-Si metasurfaces on quartz substrates, resulting in edge luminescence and weak inner signals. We present a straightforward, adjustable approach by integrating dye films on the opposite side of quartz substrates, reaching a 2.5-fold photoluminescence enhancement and improving the uniformity of the emission compared to the conventional methods. These gains stem from redirecting a significant portion of leaked fluorescence light trapped inside the substrate into free space, surpassing TIR conditions through in-plane diffraction orders of the metasurfaces across the full RGB spectrum. Our findings facilitate the design of more efficient luminescent devices.

A 85Rb transverse modulation magnetometer in the geophysical range based on atomic alignment states

Abstract We have constructed a transverse modulated magnetometer based on spin alignment in a paraffin-coated 85 Rb cell operated in a geophysical magnetic field of 47.1 µT. When an orthogonal driving magnetic field ( x ^ axis) is resonant on the Larmor frequency ( z ^ axis), we have proposed a new method to zero the static residual magnetic fields in the transverse plane and achieved a sensitivity of 1.8 pT Hz − 1 with bandwidth of 200 Hz. The repump light ( F g = 2 → F e = 2 ) redistributes the populations in the ground state, rendering the state | F g = 2 ⟩ dark. This effect significantly amplifies the optical rotation signals nearly fourfold. The numerical solution of the Liouville equation is in good agreement with the experimental results. By using perturbation treatment and employing appropriate approximations, the derived analytical expressions for optical rotation are deduced to succinctly elucidate the dynamics of atomic alignment under parametric modulation. These outcomes could be extended for the advancement of an alignment magnetometer that has been designed to detect a weak magnetic signal in the geophysical range.

Effect of saturation tone on spectral EDFA gain spectrum

Accurate characterization of spectral gain of C-band EDFAs in WDM system design is crucial; however, traditional methods often require expensive WDM equipment. This study presents a cost-effective alternative, validated through both experimental measurements and simulations, that utilizes a weak signal probe and a carefully selected saturation tone. By comparing results with a 32-channel WDM reference, we demonstrate that the proposed method achieves high accuracy. The optimal saturation tone wavelength depends on the pump wavelength (980 nm or 1480 nm) and configuration (forward or bidirectional). Nevertheless, a good fit with the reference can be obtained in all scenarios, especially at higher saturation levels. This work provides valuable insights for developing affordable and efficient EDFA gain measurement techniques.

Development of stopped-flow hyper-CEST NMR method on recirculating hyperpolarization system as applied to void space analysis in polymers.

129Xe NMR spectroscopy of polymers can provide important information on void spaces, sometimes called free volume, in polymers. Unfortunately, the spectroscopy's low sensitivity has limited its widespread use in both academic and industrial research. In order to overcome such a difficult situation, hyper-CEST method which employs hyperpolarization and CEST techniques, is examined after the introduction of recirculation and subtraction modes. Alongside the incorporated stopped-flow technique, these modes were very efficient in detecting very weak hidden signals from cellulose nanofiber (CNF) and silk fibroin (SF) films and in discussing the void space in these polymers. From the analysis of detailed saturation frequency dependence in the increment of 100Hz, the chemical shifts of hidden peaks were successfully determined to give reasonable values for the size of void space in CNF and SF. Application on thermoplastic polyurethane film also supported our method of analysis. The subtraction mode was very efficient in judging the presence or absence of any peak at a fixed saturation frequency. These facts support that the mode will surely be useful in the future exploratory study of very weak hidden signals.

Visualizing highly bright and uniform cellular ultrastructure by expansion-microscopy with tetrahedral DNA nanostructures

Expansion Microscopy (ExM) is a widely used super-resolution technique that enables imaging of structures beyond the diffraction limit of light. However, ExM suffers from weak labeling signals and expansion distortions, limiting its applicability. Here, we present an innovative approach called Tetrahedral DNA nanostructure Expansion Microscopy (TDN-ExM), addressing these limitations by using tetrahedral DNA nanostructures (TDNs) for fluorescence labeling. Our approach demonstrates a 3- to 10-fold signal amplification due to the multivertex nature of TDNs, allowing the modification of multiple dyes. Previous studies have confirmed minimal distortion on a large scale, and our strategy can reduce the distortion at the ultrastructural level in samples because it does not rely on anchoring agents and is not affected by digestion. This results in a brighter fluorescence, better uniformity, and compatibility with different labeling strategies and optical super-resolution technologies. We validated the utility of TDN-ExM by imaging various biological structures with improved resolutions and signal-to-noise ratios.

Ultrathin Indium Tin Oxide Accumulation Mode Electrolyte‐Gated Transistors for Bioelectronics

AbstractElectrolyte‐gated field effect transistors and electrochemical transistors have emerged as powerful components for bioelectronic sensors and biopotential recording devices. A set of parameters must be considered when developing devices to amplify weak electrophysiological signals. These include maximum transconductance values, cut‐off frequencies, and large on/off current ratios. Organic polymer‐based devices have recently dominated the field, especially when considering flexibility as a key factor. Oxide semiconductors may also offer these features, as well as advantages like higher mobility. Herein, flexible, ultrathin, indium tin oxide (ITO) electrolyte‐gated transistors are reported. These accumulation‐mode devices combine n‐type operation with µe = 9.5 cm2 Vs−1, high transconductance (gm = 44 mS), and on/off ratios (105) as well as optically transparent layouts. While oxides are normally considered brittle, mechanically flexible ITO layers are obtained by room temperature deposition of amorphous layers onto parylene C. This process results in low strain, producing devices that survive bending. ITO electrochemically degrades, however, with cycling. To overcome this, the surface is passivated with high dielectric constant inert capping layers of Ta2O5 or Ta2O5/AlN. This greatly improves stability while preserving low gate voltages. Based on their overall performance, ITO‐based EGFETs are promising for bioelectronics.